arXiv subjects

Michele Guindani

Publications and source records attributed to Michele Guindani.

27 records · Page 2Linked to original sources

arXiv2023

A Horseshoe mixture model for Bayesian screening with an application to light sheet fluorescence microscopy in brain imaging

In this paper, we focus on identifying differentially activated brain regions using a light sheet fluorescence microscopy - a recently developed technique for whole-brain imaging. Most existing statistical methods solve this problem by partitioning the brain regions into two classes: significantly and non-significantly activated. However, for the brain imaging problem at the center of our study, such binary grouping may provide overly simplistic discoveries by filtering out weak but important signals, that are typically adulterated by the noise present in the data. To overcome this limitation, we introduce a new Bayesian approach that allows classifying the brain regions into several tiers with varying degrees of relevance. Our approach is based on a combination of shrinkage priors - widely used in regression and multiple hypothesis testing problems - and mixture models - commonly used in model-based clustering. In contrast to the existing regularizing prior distributions, which use either the spike-and-slab prior or continuous scale mixtures, our class of priors is based on a discrete mixture of continuous scale mixtures and devises a cluster-shrinkage version of the Horseshoe prior. As a result, our approach provides a more general setting for Bayesian sparse estimation, drastically reduces the number of shrinkage parameters needed, and creates a framework for sharing information across units of interest. We show that this approach leads to more biologically meaningful and interpretable results in our brain imaging problem, since it allows the discrimination between active and inactive regions, while at the same time ranking the discoveries into clusters representing tiers of similar importance.

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arXiv2023

A Predictor-Informed Multi-Subject Bayesian Approach for Dynamic Functional Connectivity

Time Varying Functional Connectivity (TVFC) investigates how the interactions among brain regions vary over the course of an fMRI experiment. The transitions between different individual connectivity states can be modulated by changes in underlying physiological mechanisms that drive functional network dynamics, e.g., changes in attention or cognitive effort as measured by pupil dilation. In this paper, we develop a multi-subject Bayesian framework for estimating dynamic functional networks as a function of time-varying exogenous physiological covariates that are simultaneously recorded in each subject during the fMRI experiment. More specifically, we consider a dynamic Gaussian graphical model approach, where a non-homogeneous hidden Markov model is employed to classify the fMRI time series into latent neurological states, borrowing strength over the entire time course of the experiment. The state-transition probabilities are assumed to vary over time and across subjects, as a function of the underlying covariates, allowing for the estimation of recurrent connectivity patterns and the sharing of networks among the subjects. Our modeling approach further assumes sparsity in the network structures, via shrinkage priors. We achieve edge selection in the estimated graph structures, by introducing a multi-comparison procedure for shrinkage-based inferences with Bayesian false discovery rate control. We apply our modeling framework on a resting-state experiment where fMRI data have been collected concurrently with pupillometry measurements, leading us to assess the heterogeneity of the effects of changes in pupil dilation, previously linked to changes in norepinephrine-containing locus coeruleus, on the subjects' propensity to change connectivity states.

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arXiv2022

Bayesian nonparametric analysis for the detection of spikes in noisy calcium imaging data

Recent advancements in miniaturized fluorescence microscopy have made it possible to investigate neuronal responses to external stimuli in awake behaving animals through the analysis of intra-cellular calcium signals. An on-going challenge is deconvolving the temporal signals to extract the spike trains from the noisy calcium signals' time-series. In this manuscript, we propose a nested Bayesian finite mixture specification that allows the estimation of spiking activity and, simultaneously, reconstructing the distributions of the calcium transient spikes' amplitudes under different experimental conditions. The proposed model leverages two nested layers of random discrete mixture priors to borrow information between experiments and discover similarities in the distributional patterns of neuronal responses to different stimuli. Furthermore, the spikes' intensity values are also clustered within and between experimental conditions to determine the existence of common (recurring) response amplitudes. Simulation studies and the analysis of a data set from the Allen Brain Observatory show the effectiveness of the method in clustering and detecting neuronal activities.

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arXiv2021

Time-varying $\ell_0$ optimization for Spike Inference from Multi-Trial Calcium Recordings

Optical imaging of genetically encoded calcium indicators is a powerful tool to record the activity of a large number of neurons simultaneously over a long period of time from freely behaving animals. However, determining the exact time at which a neuron spikes and estimating the underlying firing rate from calcium fluorescence data remains challenging, especially for calcium imaging data obtained from a longitudinal study. We propose a multi-trial time-varying $\ell_0$ penalized method to jointly detect spikes and estimate firing rates by robustly integrating evolving neural dynamics across trials. Our simulation study shows that the proposed method performs well in both spike detection and firing rate estimation. We demonstrate the usefulness of our method on calcium fluorescence trace data from two studies, with the first study showing differential firing rate functions between two behaviors and the second study showing evolving firing rate function across trials due to learning.

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arXiv2020

A Bayesian Nonparametric model for textural pattern heterogeneity

Cancer radiomics is an emerging discipline promising to elucidate lesion phenotypes and tumor heterogeneity through patterns of enhancement, texture, morphology, and shape. The prevailing technique for image texture analysis relies on the construction and synthesis of Gray-Level Co-occurrence Matrices (GLCM). Practice currently reduces the structured count data of a GLCM to reductive and redundant summary statistics for which analysis requires variable selection and multiple comparisons for each application, thus limiting reproducibility. In this article, we develop a Bayesian multivariate probabilistic framework for the analysis and unsupervised clustering of a sample of GLCM objects. By appropriately accounting for skewness and zero-inflation of the observed counts and simultaneously adjusting for existing spatial autocorrelation at nearby cells, the methodology facilitates estimation of texture pattern distributions within the GLCM lattice itself. The techniques are applied to cluster images of adrenal lesions obtained from CT scans with and without administration of contrast. We further assess whether the resultant subtypes are clinically oriented by investigating their correspondence with pathological diagnoses. Additionally, we compare performance to a class of machine-learning approaches currently used in cancer radiomics with simulation studies.

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arXiv2020

A Common Atom Model for the Bayesian Nonparametric Analysis of Nested Data

The use of high-dimensional data for targeted therapeutic interventions requires new ways to characterize the heterogeneity observed across subgroups of a specific population. In particular, models for partially exchangeable data are needed for inference on nested datasets, where the observations are assumed to be organized in different units and some sharing of information is required to learn distinctive features of the units. In this manuscript, we propose a nested Common Atoms Model (CAM) that is particularly suited for the analysis of nested datasets where the distributions of the units are expected to differ only over a small fraction of the observations sampled from each unit. The proposed CAM allows a two-layered clustering at the distributional and observational level and is amenable to scalable posterior inference through the use of a computationally efficient nested slice-sampler algorithm. We further discuss how to extend the proposed modeling framework to handle discrete measurements, and we conduct posterior inference on a real microbiome dataset from a diet swap study to investigate how the alterations in intestinal microbiota composition are associated with different eating habits. We further investigate the performance of our model in capturing true distributional structures in the population by means of a simulation study.

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arXiv2014

Generalized Species Sampling Priors with Latent Beta reinforcements

Many popular Bayesian nonparametric priors can be characterized in terms of exchangeable species sampling sequences. However, in some applications, exchangeability may not be appropriate. We introduce a {novel and probabilistically coherent family of non-exchangeable species sampling sequences characterized by a tractable predictive probability function with weights driven by a sequence of independent Beta random variables. We compare their theoretical clustering properties with those of the Dirichlet Process and the two parameters Poisson-Dirichlet process. The proposed construction provides a complete characterization of the joint process, differently from existing work. We then propose the use of such process as prior distribution in a hierarchical Bayes modeling framework, and we describe a Markov Chain Monte Carlo sampler for posterior inference. We evaluate the performance of the prior and the robustness of the resulting inference in a simulation study, providing a comparison with popular Dirichlet Processes mixtures and Hidden Markov Models. Finally, we develop an application to the detection of chromosomal aberrations in breast cancer by leveraging array CGH data.

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arXiv2014

A hierarchical Bayesian model for inference of copy number variants and their association to gene expression

A number of statistical models have been successfully developed for the analysis of high-throughput data from a single source, but few methods are available for integrating data from different sources. Here we focus on integrating gene expression levels with comparative genomic hybridization (CGH) array measurements collected on the same subjects. We specify a measurement error model that relates the gene expression levels to latent copy number states which, in turn, are related to the observed surrogate CGH measurements via a hidden Markov model. We employ selection priors that exploit the dependencies across adjacent copy number states and investigate MCMC stochastic search techniques for posterior inference. Our approach results in a unified modeling framework for simultaneously inferring copy number variants (CNV) and identifying their significant associations with mRNA transcripts abundance. We show performance on simulated data and illustrate an application to data from a genomic study on human cancer cell lines.

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arXiv2012

A class of covariate-dependent spatiotemporal covariance functions for the analysis of daily ozone concentration

In geostatistics, it is common to model spatially distributed phenomena through an underlying stationary and isotropic spatial process. However, these assumptions are often untenable in practice because of the influence of local effects in the correlation structure. Therefore, it has been of prolonged interest in the literature to provide flexible and effective ways to model nonstationarity in the spatial effects. Arguably, due to the local nature of the problem, we might envision that the correlation structure would be highly dependent on local characteristics of the domain of study, namely, the latitude, longitude and altitude of the observation sites, as well as other locally defined covariate information. In this work, we provide a flexible and computationally feasible way for allowing the correlation structure of the underlying processes to depend on local covariate information. We discuss the properties of the induced covariance functions and methods to assess its dependence on local covariate information. The proposed method is used to analyze daily ozone in the southeast United States.

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